The goal of this Training Program is to expose graduate students to fundamental issues of macromolecular function and to develop expertise in advanced aspects of this currently exploding subject. The theme of the program is a determined focus on the chemical and mechanistic principles governing the workings of biological macromolecules, and on how their functional behaviors can be understood in terms of their molecular structures. The Training Grant will provide support for graduate students in either the Graduate Program in Biochemistry or in the Graduate Program in Biophysics, two of the five life-science graduate programs at Brandeis University. There are currently 167 students in these five programs, and we propose to support 18 on this Training Grant. Twenty faculty, all carrying out grant-funded basic research on structure and function of macromolecules, participate in this Training Program. The Program provides specific training in the following areas: protein and nucleic acid structure determination by x-ray crystallography and multidimensional NMR, high-resolution electron microscopy, mechanistic enzymology, muscle and molecular motors, membrane protein structure, protein dynamics, ion channel structure and function, and catalytic RNA mechanisms. Most graduate students in the.Program come from undergraduate backgrounds in chemistry, biochemistry, physics, or mathematics. All graduate students take a program of rigorous, quantitative courses and advanced research seminars; moreover, in the first year all students engage in intense and demanding laboratory rotations in 3-7 different laboratories. Students choose Ph.D. thesis advisors at the beginning of the second academic year and commence working on their research projects.